Analysis of joint fluid particulates has revealed collagen types I and III in patients with rheumatoid arthritis and systemic lupus erythematosus and type II in patients with severe osteoarthritis. The types and total quantity of collagen in joint fluid pellets will be correlated with the clinical diagnosis, synovial fluid oxygen partial pressure and other clinical, radiologic and serologic parameters to test the hypothesis that collagens type I and III are derived from microinfarction of the rheumatoid (or lupus) synovium. Needle-shaped hydroxyapatite crystals, active collagenase, neutral protease and particulate collagens, types I, II and III, have been found in synovial fluid from patients with severe glenohumeral osteoarthritis and rotator cuff defects. The relatively constant concentration of crystals in joint fluids obtained at intervals over a period of many months suggested that such concentrations are under homeostatic control. Synovial chondromatosis was found in one shoulder at surgery. Transmission electron microscopy showed intracellular crystal clumps suggesting that synovial cell endocytosis may provide a mechanism for crystal uptake. Addition of synthetic crystals to synovial cells in tissue culture resulted in a 5- to 8- fold increase in release of collagenase and neutral protease. Exposure of pieces of excised calcified chondromatosis tissues to partially purified mammalian collagenase released HA crystals in microspheroidal masses of identical dimensions to those seen in the patient's joint fluid. The pathogenesis of this syndrome is being investigated further.